title: Effects of the fluoroquinolone antibacterial drug ciprofloxacin on ventricular repolarization in the halothane-anesthetized Guinea pig.
abstract: The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K(+) channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6). The extents of its effects on the ventricular repolarization phase were comparable to those of another fluoroquinolone antibiotic moxifloxacin at a clinically relevant dose of 3 mg/kg (n = 6). Meanwhile, the PR interval and QRS width were also increased by ciprofloxacin at 10 mg/kg, suggesting that the drug inhibited cardiac K(+) channels as well as Na(+) and Ca(2+) channels in vivo. These results suggest that ciprofloxacin exerted a multi-ion channel-blocking action in the heart within the supra-therapeutic dose range. Therefore, careful observation may be necessary for patients with heart disease receiving a higher dose of ciprofloxacin in order to prevent the emergence of resistance.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kaori
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Naoki
authors.initials: N
authors.lastname: Omuro
authors.forename: Itsuki
authors.initials: I
authors.lastname: Kimura
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshio
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000758:Anesthesia; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006221:Halothane; D006352:Heart Ventricles / Q000187:drug effects*; D008133:Long QT Syndrome / Q000139:chemically induced; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D016276:Ventricular Function / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D002939:Ciprofloxacin; D006221:Halothane